Dose-Dependent Protective Effect of Lithium Chloride on Retinal Ganglion Cells Is Interrelated with an Upregulated Intraretinal BDNF after Optic Nerve Transection in Adult Rats

International Journal of Molecular Sciences

Ming-Mei Wu¹  Ting-Ting Zhu²  Peng Wang³  Fang Kuang¹  Ding-Jun Hao⁴  Si-Wei You¹ 

[1] Institute of Neurosciences, The Fourth Military Medical University, Xi’an 710032, China; E-Mails:;Department of Ophthalmology, General Hospital of Beijing Military Region, Beijing 100700, China; E-Mail:;Department of Obstetrics and Gynecology, General Hospital of Beijing Military Region, Beijing, 100700, China; E-Mail:;Department of Spine Surgery, Xi’an Red Cross Hospital, Xi’an 710054, China

关键词: retinal ganglion cell;    optic nerve transection;    lithium chloride;    brain-derived neurotrophic factor;    neuroprotection;   

DOI  :  10.3390/ijms150813550

来源: mdpi

【 摘 要 】

Neuroprotection of lithium for axotomized retinal ganglion cells (RGCs) is attributed to upregulated intraretinal Bcl-2. As lithium also upregulates brain-derived neurotrophic factor (BDNF) which can rescue axotomized RGCs, it is hypothesized that lithium could protect RGCs through BDNF. This study investigated this hypothesis and a possible relationship between the dose and protection of lithium. All adult experimental rats received daily intraperitoneal injections of lithium chloride (LiCl) at 30, 60 or 85 mg/kg·bw until they were euthanized 2, 7 or 14 days after left intraorbital optic nerve (ON) transection. Our results revealed that RGC densities promoted and declined with increased dose of LiCl and the highest RGC densities were always in the 60 mg/kg·bw LiCl group at both 7 and 14 day points. Similar promotion and decline in the mRNA and protein levels of intraretinal BDNF were also found at the 14 day point, while such BDNF levels increased in the 30 mg/kg·bw LiCl group but peaked in the 60 and 85 mg/kg·bw LiCl groups at the 7 day point. These findings suggested that lithium can delay the death of axotomized RGCs in a dose-dependent manner within a certain period after ON injury and such beneficial effect is interrelated with an upregulated level of intraretinal BDNF.

【 授权许可】

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© 2014 by the authors; licensee MDPI, Basel, Switzerland.